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Metabolism: Clinical and Experimental Sep 2015It has been reported that administration of octanoic acid, one of medium-chain fatty acids (MCFAs), promoted leucine oxidation in vitro and in vivo, but it remained...
OBJECTIVE
It has been reported that administration of octanoic acid, one of medium-chain fatty acids (MCFAs), promoted leucine oxidation in vitro and in vivo, but it remained unclear how octanoic acid stimulated leucine oxidation. Therefore, the aim of this study was to elucidate the mechanism that octanoic acid facilitates branched-chain amino acid (BCAA) catabolism.
MATERIALS/METHODS
In in vivo experiments, male rats were orally administered MCFAs as free fatty acids or triacylglycerol (trioctanoin), and then activities of hepatic branched-chain α-ketoacid dehydrogenase (BCKDH) complex (BCKDC) and BCKDH kinase (BDK) and alterations in the concentration of blood components were analyzed. In in vitro experiments, purified BCKDC associated with BDK (BCKDH-BDK complex) was reacted with various concentrations of hexanoic, octanoic, and decanoic acids.
RESULTS
Oral administration of trioctanoin in rats activated hepatic BCKDC via down-regulation of BDK activity in association with a decrease in plasma BCAA concentration and an increase in serum ketone body concentration. In vitro experiments using purified BCKDH-BDK complex showed that MCFAs (hexanoic, octanoic, and decanoic acids) inhibited BDK activity and that this inhibition was higher in hexanoic and octanoic acids than in decanoic acid. Oral administration of octanoic acid, but not decanoic acid, in rats activated hepatic BCKDC via down-regulation of BDK activity by decreasing the amount of BDK bound to the complex. The serum ketone body level was elevated by both administration of octanoic acid and decanoic acid.
CONCLUSION
These results suggest that octanoic acid promotes BCAA catabolism in vivo by activation of BCKDC via decreasing the bound form of BDK.
Topics: 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); Amino Acids, Branched-Chain; Animals; Caprylates; Decanoic Acids; Dose-Response Relationship, Drug; Fatty Acids, Nonesterified; Female; Ketone Bodies; Liver; Rats; Rats, Sprague-Dawley; Triglycerides
PubMed: 26104959
DOI: 10.1016/j.metabol.2015.05.014 -
Biochemical and Biophysical Research... Sep 2018Olfactory receptors (ORs) are G protein-coupled receptors that mediate olfactory chemosensation, leading to the perception of smell. ORs are expressed in many tissues,...
Olfactory receptors (ORs) are G protein-coupled receptors that mediate olfactory chemosensation, leading to the perception of smell. ORs are expressed in many tissues, but their functions are largely unknown. Here, we show that the olfactory receptor Olfr15 is highly and selectively expressed in both mouse pancreatic β-cells and MIN6 cells. In addition, octanoic acid (OA), a medium-chain fatty acid, potentiates glucose-stimulated insulin secretion (GSIS). The OA-induced enhancement of GSIS was inhibited by Olfr15 knockdown. Treatment with a PLC inhibitor or an Ins(1,4,5)P receptor (IPR) antagonist also blocked the OA-induced enhancement of GSIS. These results suggest that OA potentiates GSIS via Olfr15 though the PLC-IP pathway. Furthermore, long-term treatment with OA increased cellular glucose uptake in MIN6 cells by up-regulating the expression of glucokinase (GK). Moreover, this process was blocked by an IPR antagonist and a Ca/calmodulin-dependent protein kinase kinase (CaMKK) inhibitor. Similarly, OA stimulated GK promoter activity, while either Olfr15 or CaMKIV knockdown blocked the stimulatory effect of OA on GK promoter activity. These results suggest that long-term treatment of OA induces GK promoter activity via Olfr15 through the IP-CaMKK/CaMKIV pathway. In islets from type 2 diabetic mice, the expression level of Olfr15 and the OA-induced enhancement of GSIS were strongly reduced. Collectively, our results highlight the crucial role of the olfactory receptor Olfr15 in potentiating GSIS in pancreatic β-cells, suggesting that Olfr15 may be an important therapeutic target in type 2 diabetes.
Topics: Animals; Caprylates; Cell Line; Cells, Cultured; Diabetes Mellitus, Type 2; Functional Food; Gene Expression Regulation; Glucokinase; Glucose; Insulin; Insulin-Secreting Cells; Male; Mice; Mice, Inbred C57BL; Receptors, Odorant; Signal Transduction
PubMed: 29885841
DOI: 10.1016/j.bbrc.2018.06.015 -
The Journal of Endocrinology May 2020Circulating growth hormone (GH) concentrations increase during pregnancy in mice and remain pituitary-derived. Whether abundance or activation of the GH secretagogue...
Circulating growth hormone (GH) concentrations increase during pregnancy in mice and remain pituitary-derived. Whether abundance or activation of the GH secretagogue ghrelin increase during pregnancy, or in response to dietary octanoic acid supplementation, is unclear. We therefore measured circulating GH profiles in late pregnant C57BL/6J mice and in aged-matched non-pregnant females fed with standard laboratory chow supplemented with 5% octanoic or palmitic (control) acid (n = 4-13/group). Serum total and acyl-ghrelin concentrations, stomach and placenta ghrelin mRNA and protein expression, Pcsk1 (encoding prohormone convertase 1/3) and Mboat4 (membrane bound O-acyl transferase 4) mRNA were determined at zeitgeber (ZT) 13 and ZT23. Total and basal GH secretion were higher in late pregnant than non-pregnant mice (P < 0.001), regardless of diet. At ZT13, serum concentrations of total ghrelin (P = 0.004), but not acyl-ghrelin, and the density of ghrelin-positive cells in the gastric antrum (P = 0.019) were higher, and gastric Mboat4 and Pcsk1 mRNA expression were lower in pregnant than non-pregnant mice at ZT23. In the placenta, ghrelin protein was localised mostly to labyrinthine trophoblast cells. Serum acyl-, but not total, ghrelin was lower at mid-pregnancy than in non-pregnant mice, but not different at early or late pregnancy. In conclusion, dietary supplementation with 5% octanoic acid did not increase activation of ghrelin in female mice. Our results further suggest that increases in maternal GH secretion throughout murine pregnancy are not due to circulating acyl-ghrelin acting at the pituitary. Nevertheless, time-dependent increased circulating total ghrelin could potentially increase ghrelin action in tissues that express the acylating enzyme and receptor.
Topics: Acylation; Animals; Caprylates; Dietary Supplements; Female; Gastric Mucosa; Ghrelin; Growth Hormone; Mice; Mice, Inbred C57BL; Placenta; Pregnancy; RNA, Messenger
PubMed: 32176867
DOI: 10.1530/JOE-20-0072 -
Neurochemical Research Jan 2023Ketogenic diets and medium-chain triglycerides are gaining attention as treatment of neurological disorders. Their major metabolites, β-hydroxybutyrate (βHB) and the...
Ketogenic diets and medium-chain triglycerides are gaining attention as treatment of neurological disorders. Their major metabolites, β-hydroxybutyrate (βHB) and the medium-chain fatty acids (MCFAs) octanoic acid (C8) and decanoic acid (C10), are auxiliary brain fuels. To which extent these fuels compete for metabolism in different brain cell types is unknown. Here, we used acutely isolated mouse cerebral cortical slices to (1) compare metabolism of 200 µM [U-C]C8, [U-C]C10 and [U-C]βHB and (2) assess potential competition between metabolism of βHB and MCFAs by quantifying metabolite C enrichment using gas chromatography-mass spectrometry (GC-MS) analysis. The C enrichment in most metabolites was similar with [U-C]C8 and [U-C]C10 as substrates, but several fold lower with [U-C]βHB. The C enrichment in glutamate was in a similar range for all three substrates, whereas the C enrichments in citrate and glutamine were markedly higher with both [U-C]C8 and [U-C]C10 compared with [U-C]βHB. As citrate and glutamine are indicators of astrocytic metabolism, the results indicate active MCFA metabolism in astrocytes, while βHB is metabolized in a different cellular compartment. In competition experiments, C-βHB altered C incorporation from [U-C]C8 and [U-C]C10 in only a few instances, while C-C8 and C-C10 only further decreased the low [U-C]βHB-derived C incorporation into citrate and glutamine, signifying little competition for oxidative metabolism between βHB and the MCFAs. Overall, the data demonstrate that βHB and MCFAs are supplementary fuels in different cellular compartments in the brain without notable competition. Thus, the use of medium-chain triglycerides in ketogenic diets is likely to be beneficial in conditions with carbon and energy shortages in both astrocytes and neurons, such as GLUT1 deficiency.
Topics: Animals; Mice; 3-Hydroxybutyric Acid; Glutamine; Fatty Acids; Citrates; Triglycerides; Cerebral Cortex
PubMed: 35999339
DOI: 10.1007/s11064-022-03726-6 -
Journal of Biochemistry Oct 2016In the gastric peptide hormone ghrelin, serine 3 (threonine 3 in frogs) is modified, primarily by n-octanoic acid; this modification is essential for ghrelin's activity.... (Review)
Review
In the gastric peptide hormone ghrelin, serine 3 (threonine 3 in frogs) is modified, primarily by n-octanoic acid; this modification is essential for ghrelin's activity. The enzyme that transfers n-octanoic acid to Ser3 of ghrelin is ghrelin O-acyltransferase (GOAT). GOAT, the only enzyme known to catalyze acyl modification of ghrelin, specifically modifies serine (or threonine) at the third position and does not modify other serine residues in ghrelin peptides. GOAT prefers n-hexanoyl-CoA over n-octanoyl-CoA as the acyl donor, although in the stomach the n-octanoyl form is the predominant form of acyl-modified ghrelin. GOAT is a promising target for drug development to treat metabolic diseases and eating disorders.
Topics: Acyltransferases; Animals; Fatty Acids; Ghrelin; Humans; Lipoylation; Substrate Specificity
PubMed: 27489223
DOI: 10.1093/jb/mvw046 -
Physical Chemistry Chemical Physics :... Mar 2022Alpha-keto acids are environmentally and biologically relevant species whose chemistry has been shown to be influenced by their local environment. Vibrational...
Alpha-keto acids are environmentally and biologically relevant species whose chemistry has been shown to be influenced by their local environment. Vibrational spectroscopy provides useful ways to probe the potential inter- and intramolecular interactions available to them in several phases. We measure and compare the IR spectra of 2-oxo-octanoic acid (2OOA) in the gas phase, solid phase, and at the air-water interface. With theoretical support, we assign many of the vibrational modes in each of the spectra. In the gas phase, two types of conformers are identified and distinguished, with the intramolecularly H-bonded form being the dominant type, while the second conformer type identified does not have an intramolecular hydrogen bond. The van der Waals interactions between molecules in solid 2OOA manifest C-H and CO vibrations lower in energy than in the gas phase and we propose an intermolecular hydrogen bonding scheme for the solid phase. At the air-water interface the hydrocarbon tails of 2OOA do interact with each other while the carbonyls appear to interact with water in the subphase, but not with neighboring 2OOA as might be expected of a closely packed surfactant film.
Topics: Caprylates; Hydrogen Bonding; Spectrophotometry, Infrared; Vibration; Water
PubMed: 35237773
DOI: 10.1039/d1cp05345k -
Environmental Technology Mar 2021Anoxic co-biodegradation of linear and cyclic naphthenic acids (NAs) namely octanoic acid, trans-4-methyl-1-cyclohexane carboxylic acid (trans-4MCHCA), cis- and...
Anoxic co-biodegradation of linear and cyclic naphthenic acids (NAs) namely octanoic acid, trans-4-methyl-1-cyclohexane carboxylic acid (trans-4MCHCA), cis- and trans-4-methyl-1-cyclohexane-acetic acids (cis-4MCHAA and trans-4MCHAA) was investigated in denitrifying biofilm reactors. In all evaluated compositions, co-biodegradation of NAs was coupled to denitrification, with octanoic acid showing the fastest biodegradation rate (1180.4 mg L h at loading rate of 1180.4 mg L h), followed by trans-4MCHCA (398.1 mg L h at loading rate of 435.8 mg L h), trans-4MCHAA (25.7 mg L h at loading rate of 221.7 mg L h), and cis-4MCHAA (5.3 mg L h at loading rate of 16.9 mg L h). Biodegradation of octanoic acid and trans-4MCHCA were not influenced by the presence of recalcitrant NAs (cis- and trans-4MCHAA). Co-biodegradation of cis- and trans-4MCHAA with octanoic acid, trans-4MCHCA, or their combination enhanced the biodegradability of these recalcitrant NAs, with the positive impact being more pronounced for trans-4MCHCA. Finally anoxic co-biodegradation of NAs under denitrifying conditions proceeded at rates that were faster than the aerobic rates obtained in similar mixtures. Anoxic biodegradation, therefore, is an effective alternative for in situ treatment of oil sands process water in anoxic stabilization ponds amended with nitrate, or as an ex situ treatment approach in denitrifying bioreactors whereby the cost and technical challenges of aeration are eliminated.
Topics: Biodegradation, Environmental; Biofilms; Carboxylic Acids; Oil and Gas Fields; Water Pollutants, Chemical
PubMed: 31378149
DOI: 10.1080/09593330.2019.1650122 -
Foods (Basel, Switzerland) Feb 2023The solid-state fermentation of Baijiu is complicated by the co-fermentation of many microorganisms. The instability of the composition and abundance of the...
The solid-state fermentation of Baijiu is complicated by the co-fermentation of many microorganisms. The instability of the composition and abundance of the microorganisms in the fermentation process leads to fluctuations of product quality, which is one of the bottleneck problems faced by the Strong-flavor Baijiu industry. In this study, we established a combination of functional microorganisms for the stable fermentation of the main flavor compounds of Baijiu, including medium and long-chain fatty acid ethyl esters such as hexanoic acid, ethyl ester; butanoic acid, ethyl ester; octanoic acid, ethyl ester; acetic acid, ethyl ester; 9,12-octadecadienoic acid, ethyl ester; and decanoic acid, ethyl ester in the fermented grains. Our study investigated the effects of microbial combinations on the fermentation from three aspects: microbial composition, microbial interactions, and microbial association with flavor compounds. The results showed that the added functional microorganisms (, , , , and ) became the dominant species in the fermentation system and formed positive interactions with other microorganisms, while the negative interactions between microorganisms were significantly reduced in the fermentation systems that contained both Daqu and functional microorganisms. The redundancy analysis showed that the functional microorganisms (, , , , , , and ) showed strong positive correlations with the main flavor compounds (hexanoic acid, ethyl ester; lactic acid, ethyl ester; butanoic acid, ethyl ester; acetic acid, ethyl ester; and octanoic acid, ethyl ester). These results indicated that it was feasible to produce Baijiu with a functional microbial combination, and that this could promote stable Baijiu production.
PubMed: 36766173
DOI: 10.3390/foods12030644 -
World Journal of Gastrointestinal... Aug 2016In the field of gastroenterology, breath tests (BTs) are used intermittently as diagnostic tools that allow indirect, non-invasive and relatively less cumbersome... (Review)
Review
In the field of gastroenterology, breath tests (BTs) are used intermittently as diagnostic tools that allow indirect, non-invasive and relatively less cumbersome evaluation of several disorders by simply quantifying the appearance in exhaled breath of a metabolite of a specific substrate administered. The aim of this review is to have an insight into the principles, methods of analysis and performance parameters of various hydrogen, methane and carbon BTs which are available for diagnosing gastrointestinal disorders such as Helicobacter pylori infection, small intestinal bacterial overgrowth, and carbohydrate malabsorption. Evaluation of gastric emptying is routinely performed by scintigraphy which is however, difficult to perform and not suitable for children and pregnant women, this review has abridged the 13C-octanoic acid test in comparison to scintigraphy and has emphasized on its working protocol and challenges. A new development such as electronic nose test is also highlighted. Moreover we have also explored the limitations and constraints restraining the wide use of these BT. We conclude that breath testing has an enormous potential to be used as a diagnostic modality. In addition it offers distinct advantages over the traditional invasive methods commonly employed.
PubMed: 27574563
DOI: 10.4291/wjgp.v7.i3.256 -
Journal of Dairy Science Nov 2019To determine the key aroma compounds in Chinese milk fan cheese, samples from 6 of the most popular handmade milk fan workshops in Yunnan province of China were analyzed...
To determine the key aroma compounds in Chinese milk fan cheese, samples from 6 of the most popular handmade milk fan workshops in Yunnan province of China were analyzed by gas chromatography-mass spectrometry (GC-MS), gas chromatography-olfactometry (GC-O), sensory evaluation, aroma recombination and omission experiments. Seventy-one aroma compounds were identified by GC-MS, and 31 odor-active compounds were detected by GC-O. The relationships between the 31 odor-active compounds and 10 sensory evaluation properties were explored by partial least squares discriminant analysis. The results identified 23 initial key aroma compounds, which were used to simulate the aroma profile of milk fan in aroma recombination experiments. Aroma omission experiments identified propanoic acid, butanoic acid, octanoic acid, octanal, nonanal, 2-nonanone, and ethyl hexanoate as the key aroma compounds. Propanoic acid and butanoic acid contributed to cheese and rancid aromas, octanal and nonanal to the fat aroma, octanoic acid and 2-nonanone to the cheese aroma, and ethyl hexanoate to the fruity aroma of milk fan.
Topics: Aldehydes; Animals; Cattle; Cheese; China; Gas Chromatography-Mass Spectrometry; Ketones; Least-Squares Analysis; Milk; Odorants; Olfactometry
PubMed: 31477286
DOI: 10.3168/jds.2019-16796